title: Immunity to HIV-1 is influenced by continued natural exposure to exogenous virus.
abstract: Unprotected sexual intercourse between individuals who are both infected with HIV-1 can lead to exposure to their partner's virus, and potentially to super-infection. However, the immunological consequences of continued exposure to HIV-1 by individuals already infected, has to our knowledge never been reported. We measured T cell responses in 49 HIV-1 infected individuals who were on antiretroviral therapy with suppressed viral loads. All the individuals were in a long-term sexual partnership with another HIV-1 infected individual, who was either also on HAART and suppressing their viral loads, or viremic (>9000 copies/ml). T cell responses to HIV-1 epitopes were measured directly ex-vivo by the IFN-gamma enzyme linked immuno-spot assay and by cytokine flow cytometry. Sexual exposure data was generated from questionnaires given to both individuals within each partnership. Individuals who continued to have regular sexual contact with a HIV-1 infected viremic partner had significantly higher frequencies of HIV-1-specific T cell responses, compared to individuals with aviremic partners. Strikingly, the magnitude of the HIV-1-specific T cell response correlated strongly with the level and route of exposure. Responses consisted of both CD4(+) and CD8(+) T cell subsets. Longitudinally, decreases in exposure were mirrored by a lower T cell response. However, no evidence for systemic super-infection was found in any of the individuals. Continued sexual exposure to exogenous HIV-1 was associated with increased HIV-1-specific T cell responses, in the absence of systemic super-infection, and correlated with the level and type of exposure.
authors.affiliation: Division of Experimental Medicine, Department of Medicine, University of California San Francisco, San Francisco, California, USA. Chris.Willberg@ndm.ox.ac.uk
authors.forename: Christian B
authors.initials: CB
authors.lastname: Willberg
authors.forename: J Jeff
authors.initials: JJ
authors.lastname: McConnell
authors.forename: Emily M
authors.initials: EM
authors.lastname: Eriksson
authors.forename: Larry A
authors.initials: LA
authors.lastname: Bragg
authors.forename: Vanessa A
authors.initials: VA
authors.lastname: York
authors.forename: Teri J
authors.initials: TJ
authors.lastname: Liegler
authors.forename: Fredrick M
authors.initials: FM
authors.lastname: Hecht
authors.forename: Robert M
authors.initials: RM
authors.lastname: Grant
authors.forename: Douglas F
authors.initials: DF
authors.lastname: Nixon
mesh_terms: D017088:AIDS-Related Opportunistic Infections / Q000276:immunology* / Q000821:virology*; D000328:Adult; D023241:Antiretroviral Therapy, Highly Active; D015331:Cohort Studies; D015658:HIV Infections / Q000150:complications / Q000188:drug therapy / Q000276:immunology* / Q000821:virology; D015497:HIV-1 / Q000235:genetics / Q000276:immunology* / Q000502:physiology; D006801:Humans; D007371:Interferon-gamma / Q000097:blood; D010802:Phylogeny; D012725:Sexual Behavior / Q000502:physiology; D012747:Sexual Partners; D015163:Superinfection / Q000276:immunology / Q000821:virology; D013601:T-Lymphocytes / Q000276:immunology; D047568:Unsafe Sex / Q000502:physiology / Q000706:statistics & numerical data; D014766:Viremia / Q000276:immunology; D014777:Virus Diseases / Q000150:complications / Q000276:immunology* / Q000821:virology
chemical_list: D007371:Interferon-gamma